Insulin resistance negatively affects bone quality not quantity: the relationship between bone and adipose tissue.

The present study suggests that insulin resistance has no association with bone quantity, but quality. INTRODUCTION: The literature has contradictory results concerning the influence of insulin resistance on bone. The present study sought to evaluate the association of insulin resistance and adipose tissue with either bone mineral density or the trabecular bone score. METHODS: The study included 56 individuals (36 women and 20 men): age = 46.6 ± 14.2 years, weight = 67.8 ± 10.9 kg, height = 1.65 ± 0.10 m and BMI = 24.8 ± 3.9 kg/m2. The investigational protocol included biochemical determinations and bone assessment by dual X-ray absorptiometry for evaluation of bone mineral density and trabecular bone score. Magnetic resonance was employed to estimate visceral, subcutaneous and bone marrow adipose tissues, as well as intrahepatic lipids. RESULTS: The bone mineral density of the lumbar spine, femoral neck and total hip were not associated with insulin resistance-related parameters [visceral adipose tissue, intrahepatic lipids and homeostatic model assessment of insulin resistance (HOMA-IR)]. In contrast, there was a negative relationship between the trabecular bone score and all these components. The association between the trabecular bone score and HOMA-IR was reinforced after adjustment for age and BMI. Marrow adipose tissue was negatively associated with both bone mineral density and trabecular bone score. CONCLUSIONS: The present study shows that the trabecular bone score is negatively associated with marrow adipose tissue, insulin resistance, visceral adipose tissue and intrahepatic lipid measurements. Additionally, there was a negative relationship between saturated lipids in marrow adipose tissue and the trabecular bone score. These results encourage further studies to investigate the role of the trabecular bone score exam in the clinical evaluation of osteoporosis in conditions of insulin resistance.

Reduced bone mass and preserved marrow adipose tissue in patients with inflammatory bowel diseases in long-term remission.

Bone marrow adipose tissue has not been studied in patients with inactive inflammatory bowel disease. We found that these patients have preserved marrow adiposity even with low bone mass. Factors involved in bone loss in active disease may have long-lasting effects but do not seem to affect bone marrow adiposity. INTRODUCTION: Reduced bone mass is known to occur at varying prevalence in patients with inflammatory bowel diseases (IBD) because of inflammation, malnutrition, and steroid therapy. Osteoporosis may develop in these patients as the result of an imbalanced relationship between osteoblasts and adipocytes in bone marrow. This study aimed to evaluate for the first time bone mass and bone marrow adipose tissue (BMAT) in a particular subgroup of IBD patients characterized by long-term, steroid-free remission. METHODS: Patients with Crohn's disease (CD; N = 21) and ulcerative colitis (UC; N = 15) and controls (C; N = 65) underwent dual X-ray energy absorptiometry and nuclear magnetic resonance spectroscopy of the L3 lumbar vertebra for BMAT assessment. RESULTS: Both the CD and UC subgroups showed significantly higher proportions of patients than controls with Z-score ≤-2.0 at L1-L4 (C 1.54%; CD 19.05%; UC 20%; p = 0.02), but not at other sites. The proportions of CD patients with a T-score ˂-1.0 at the femoral neck (C 18.46%; CD 47.62%; p = 0.02) and total hip (C 16.92%; CD 42.86%; p = 0.03) were significantly higher than among controls. There were no statistically significant differences between IBD patients and controls regarding BMAT at L3 (C 28.62 ± 8.15%; CD 29.81 ± 6.90%; UC 27.35 ± 9.80%; p = 0.67). CONCLUSIONS: IBD patients in long-term, steroid-free remission may have a low bone mass in spite of preserved BMAT. These findings confirm the heterogeneity of bone disorders in IBD and may indicate that factors involved in bone loss in active disease may have long-lasting effects on these patients.

Jumping exercise preserves bone mineral density and mechanical properties in osteopenic ovariectomized rats even following established osteopenia.

The effects of jump training on bone structure before and after ovariectomy-induced osteopenia in rats were investigated. Jumping exercise induced favorable changes in bone mineral density, bone mechanical properties, and bone formation/resorption markers. This exercise is effective to prevent bone loss after ovariectomy even when osteopenia is already established. INTRODUCTION: The present study investigated the effects of jump training on bone structure before and after ovariectomy-induced osteopenia in 80 10-week-old Wistar rats. METHODS: Forty rats (prevention program) were randomly allocated to one of four equal groups (n = 10): sham-operated sedentary (SHAM-SEDp), ovariectomized (OVX) sedentary (OVX-SEDp), sham-operated exercised (SHAM-EXp), and OVX exercised (OVX-EXp). SHAM-EXp and OVX-EXp animals began training 3 days after surgery. Another 40 rats (treatment program) were randomly allocated into another four groups (n = 10): sham-operated sedentary (SHAM-SEDt), OVX sedentary (OVX-SEDt), sham-operated exercised (SHAM-EXt), and OVX exercised (OVX-EXt). SHAM-EXt and OVX-EXt animals began training 60 days after surgery. The rats in the exercised groups jumped 20 times/day, 5 days/week, to a height of 40 cm for 12 weeks. At the end of the experimental period, serum osteocalcin, follicle-stimulating hormone (FSH) dosage, dual X-ray absorptiometry (DXA), histomorphometry, and biomechanical tests were analyzed. RESULTS: The OVX groups showed higher values of FSH and body weight (p < 0.05). DXA showed that jump training significantly increased bone mineral density of the femur and fifth lumbar vertebra (p < 0.05). The stiffness of the left femur and fifth lumbar vertebra in the exercised groups was greater than that of the sedentary groups (p < 0.05). Ovariectomy induced significant difference in bone volume (BV/TV, percent), trabecular separation (Tb.Sp, micrometer), and trabecular number (Tb.N, per millimeter) (p < 0.05) compared to sham operation. Jump training in the OVX group induced significant differences in BV/TV, Tb.Sp, and Tb.N and decreased osteoblast number per bone perimeter (p < 0.05) compared with OVX nontraining, in the prevention groups. Osteocalcin dosage showed higher values in the exercised groups (p < 0.05). CONCLUSIONS: Jumping exercise induced favorable changes in bone mineral density, bone mechanical properties, and bone formation/resorption markers. Jump training is effective to prevent bone loss after ovariectomy even when osteopenia is already established.

The osteogenic effects of swimming, jumping, and vibration on the protection of bone quality from disuse bone loss.

We assessed and compared the effects of swimming, jumping, and vibration therapies on the prevention of bone loss because of unloading. Eighty Wistar rats were randomly divided into eight groups: S, permanent hind limb-suspended rats; CON, control rats; S + Swim, unloading interrupted by swimming exercise; S + C(Swim), suspension interrupted by regular weight-bearing with the same duration as in the S + Swim protocol; S + Jump, unloading interrupted by jumping exercise; S + C(Jump), suspension interrupted for regular weight-bearing as in the S + Jump group; S + Vibr, unloading interrupted by vibration; and S + C(Vibr), suspension with interruptions for regular weight-bearing with the same protocol as that used for the S + Vibr rats. At the end of the experiment, the bone mineral density, bone strength, histomorphometric parameters, and serum levels of the bone markers were analyzed. The hind limb-suspended rats exhibited bone quality loss. In contrast, the trained rats showed a significant increase in bone mass, bone strength, bone formation, and serum levels of bone markers compared with the respective controls. Although we did not find a significant difference among the three physical exercises, the osteogenic effect of vibration was slightly lower than that of swimming and jumping. Thus, all physical exercises were efficient in preventing bone loss because of unloading and preserving bone quality.

Features of lumbar spine texture extracted from routine MRI correlate with bone mineral density and can potentially differentiate patients with and without fragility fractures in the spine.

The use of routine magnetic resonance imaging (MRI) to potentially assess skeletal fragility has been widely studied in osteoporosis. The aim of this study was to evaluate bone texture attributes (TA) from routine lumbar spine (LS) MRI and their correlation with vertebral fragility fractures (VFF) and bone mineral density (BMD). Sixty-four post-menopausal women were submitted to LS densitometry, total spine radiographs, and routine T2-weighted LS MRI. Twenty-two TA were extracted with the platform IBEX from L3 vertebra. The statistical difference was evaluated using ANOVA and Duncan's post-test. Correlation analyses were performed using Spearman's coefficient. Statistical significance was considered when P<0.05. The results did not show a significant difference in BMD between the women with and without fractures. Two bone TA (cluster tendency and variance) were significantly lower in the fracture group. Cluster tendency with VFF in osteopenia was 1.54±1.37 and in osteoporosis was 1.11±58. Cluster tendency without VFF in osteopenia was 2.23±1.38 and in osteoporosis was 1.88±1.14). Variance with VFF in osteopenia was 1.44±1.37 and in osteoporosis was 1.13±59. Variance without VFF in osteopenia was 2.34±1.38 and in osteoporosis was 1.89±1.14. There was a significant correlation between BMD and cluster prominence (r=0.409), cluster tendency (r=0.345), correlation (r=0.570), entropy (r=0.364), information measure corr1 (r=0.378), inverse variance (r=0.449), sum entropy (r=0.320), variance (r=0.338), sum average (r=-0.274), and sum variance (r=-0.266). Our results demonstrated the potential use of TA extracted from routine MRI as a biomarker to assess osteoporosis and identify the tendency of skeletal fragility vertebral fractures.

New insights into osteoporosis: the bone-fat connection.

Osteoporosis and obesity are chronic disorders that are both increasing in prevalence. The pathophysiology of these conditions is multifactorial and includes genetic, environmental and hormonal determinants. Although it has long been considered that these are distinct disorders rarely found in the same individual, emerging evidence from basic and clinical studies support an important interaction between adipose tissue and the skeleton. It is proposed that adiposity may influence bone remodelling through three mechanisms: (i) secretion of cytokines that directly target bone, (ii) production of adipokines that influence the central nervous system thereby changing sympathetic impulses to bone and (iii) paracrine influences on adjacent skeletal cells. Here we focus on the current understanding of bone-fat interactions and the clinical implications of recent studies linking obesity to osteoporosis.

Hashtag bone: detrimental effects on bone contrast with metabolic benefits one and five years after Roux-en-Y gastric bypass.

Bone loss is a potential adverse consequence of rapid and sustained weight loss after bariatric surgery. The aim of the present study was to evaluate the bone mass, body fat distribution, and metabolic parameters in women submitted to Roux-en-Y gastric bypass (RYGB). The study included the following three groups: one group of lean women (control [C] group) and two groups of obese women, one evaluated one year (B1) and the other five years (B5) after RYGB. Dual-energy X-ray absorptiometry and magnetic resonance imaging were used to determine bone mineral density (BMD; lumbar spine, total hip, and femoral neck) and abdominal fat content (subcutaneous [SAT] and visceral [VAT] adipose tissues, and intrahepatic lipids [IHL]). The BMD/body mass index ratio was lower in the B5 compared with the C group at all sites. Serum C-terminal telopeptide of type I collagen (CTX) levels were higher in the B1 and B5 groups compared with the C group. Individuals submitted to RYGB showed greater SAT but similar VAT and IHL values compared with those in the C group. However, the B5 group had higher mean parathyroid hormone levels compared with the other two groups. Individuals submitted to RYGB presented increased levels of CTX and low BMD for body weight than those in the C group, suggesting that bone catabolism is a persistent alteration associated with RYGB. In conclusion, the long-lasting metabolic benefits obtained with RYGB in obesity are counterbalanced by a persistent catabolic effect of the procedure on bone and mineral metabolism.

Elongated styloid process and atheroma in panoramic radiography and its relationship with systemic osteoporosis and osteopenia.

UNLABELLED: Association between the presence of an elongated styloid process, vascular calcification (atheroma) and the potential risk factor for osteoporosis was studied. Presence of an elongated styloid process was found to be correlated with systemic osteoporosis and also between elongated styloid process and atheroma. INTRODUCTION: The association between the presences of an elongated styloid process and vascular calcification (atheroma) with the potential risk factor assessment for osteoporosis was studied. METHODS: Bone mineral density obtained by dual energy X-ray absorptiometry diagnosed osteopenia/osteoporosis on at least two of three sites (column, hips, and forearm) of 50 female patients. Panoramic maxillomandibular radiographs were taken and analyzed. Elongation of the styloid processes was measured and the presence of atheromas in the carotid was investigated. RESULTS: Eighty percent of the patients presented at least one side with elongated styloid process and the highest prevalence (87.5%) occurred in individuals between 60 and 69 years. Atheroma was found in four patients, three of which presented elongated styloid on at least one side and had diagnosed osteoporosis on at least two of the evaluated sites. CONCLUSIONS: Correlation was found between the elongation of the styloid process and systemic osteoporosis, and between elongated styloid process and atheroma. The method in this study might be used as part of a method for osteopenia/osteoporosis and atheroma risk assessment.

Back to the future: revisiting parathyroid hormone and calcitonin control of bone remodeling.

This review reflects on the past, present, and future of translational research on calcitropic hormones and bone metabolism. Calcitonin (CT) and parathormone (PTH) are complementary hormones involved in the acquisition and maintenance of bone mass and regulation of calcium metabolism. Early research demonstrated that these hormones could have an important role in the treatment of osteoporosis. Calcitonin was approved for this indication by the FDA more than two decades ago, and PTH gained regulatory approval for the treatment of osteoporosis nearly ten years ago. Unfortunately, basic research underlying the mechanism of action of these agents has lagged behind drug approval, and the role of these hormones in bone remodeling is still not firmly established. Moreover, research in bone biology shifted from these hormones to smaller molecules and paracrine regulators of skeletal remodeling. Although important, this development was somewhat unfortunate because without a clearer understanding of how calcitropic hormones work, we cannot be sure that they are being used optimally in the management of osteoporosis. In this review, we look at what is known about CT and PTH and the cells that they target, namely osteoblasts, osteoclasts, and osteocytes. We then identify gaps in knowledge and the research needed to fill them. The conduct of mechanistic studies may point to important factors, such as diurnal variation and dose responsiveness that would lead to improved treatment regimens. By reopening lines of basic and clinical investigation and applying those findings at the bedside, we hope to restart the cycle of translational research in this area.

Effect of fluid and food intake on the body composition evaluation of elderly persons.

BACKGROUND: Several studies have shown that liquid and food intake interfere with the evaluation of body composition in adults. However, since there are no reports about this interference in the elderly population, the need to fast for this evaluation may be dispensable. OBJECTIVES: The objective of the present study was to assess the influence of liquid and solid food on the measurement of body composition by bioelectrical impedance analysis (BIA) and by dual energy X-ray absorptiometry (DXA). DESIGN: Forty-one male volunteers aged 62 to 87 years participated in the study. The subjects were submitted to evaluation of body composition by DXA and BIA under fasting conditions and 1 hour after the ingestion of breakfast (500 ml of orange juice and one 50 g bread roll with butter). RESULTS: There was no significant difference in the variables fat-free mass (FFM) or fat mass (FM) between the fasting condition and the evaluation performed 1 hour after the meal as measured by BIA or DXA. There was also no significant difference when the same variables were compared between methods. CONCLUSION: In the present study, the ingestion of 500 ml orange juice and of one bread roll with butter by elderly subjects did not affect the results of the parameters of body composition determined by BIA or DXA. Thus, these exams could be performed without the rigor of fasting, often poorly tolerated by the elderly.

Renal developmental disturbances and their long-term consequences in female pups from vitamin D-deficient mothers: involved mechanisms.

The mechanisms involved in kidney disturbances during development, induced by vitamin D3 deficiency in female rats, that persist into adulthood were evaluated in this study. Female offspring from mothers fed normal (control group, n=8) or vitamin D-deficient (Vit.D-, n=10) diets were used. Three-month-old rats had their systolic blood pressure (SBP) measured and their blood and urine sampled to quantify vitamin D3 (Vit.D3), creatinine, Na+, Ca+2 and angiotensin II (ANGII) levels. The kidneys were then removed for nitric oxide (NO) quantification and immunohistochemical studies. Vit.D- pups showed higher SBP and plasma ANGII levels in adulthood (P<0.05) as well as decreased urine osmolality associated with increases in urinary volume (P<0.05). Decreased expression of JG12 (renal cortex and glomeruli) and synaptopodin (glomeruli) as well as reduced renal NO was also observed (P<0.05). These findings showed that renal disturbances in development in pups from Vit.D- mothers observed in adulthood may be related to the development of angiogenesis, NO and ANGII alterations.

Parathyroid hormone secretion in women in late menopause submitted to EDTA-induced hypocalcemia.

OBJECTIVE: The physiological role of parathormone (PTH) in the maintenance of bone mass in humans has not been fully defined. The main objective of the present study was to evaluate basal and EDTA-stimulated PTH levels in young women (Group Y=30.9 years, N=7) and in women in late menopause (Group M=64.7 years, N=7) and their relationship to bone mineral density. METHODS: The PTH secretion test was performed by induction of hypocalcemia through intravenous administration of EDTA for 2h. Blood samples were collected every 10 min and used for ionic calcium and PTH measurements. During the basal period, an additional sample was collected for the determination of osteocalcin, FSH, and estradiol. A sample of early morning second voided urine was collected for analysis of deoxypiridinoline and creatinine as well as bone mass density (BMD) was determined by dual X-ray energy absorptiometry (DEXA). RESULTS: The aged patients presented lower femoral BMD (Y=0.860 g/cm(2) vs. M=0.690 g/cm(2), p<0.01), with four of them having a T score lower than -2.5 S.D. Basal, and during the EDTA infusion, PTH values were similar in both groups. However, among aged volunteers, the rise in PTH levels was higher for subjects with normal bone mass (NM: peak=236 pg/ml) than for subjects with osteoporosis (OM: peak=134.4 pg/ml). CONCLUSIONS: The present results suggest that PTH can have a modulating effect on the rate of bone loss during late menopause.

Features of lumbar spine texture extracted from routine MRI correlate with bone mineral density and can potentially differentiate patients with and without fragility fractures in the spine

The use of routine magnetic resonance imaging (MRI) to potentially assess skeletal fragility has been widely studied in osteoporosis. The aim of this study was to evaluate bone texture attributes (TA) from routine lumbar spine (LS) MRI and their correlation with vertebral fragility fractures (VFF) and bone mineral density (BMD). Sixty-four post-menopausal women were submitted to LS densitometry, total spine radiographs, and routine T2-weighted LS MRI. Twenty-two TA were extracted with the platform IBEX from L3 vertebra. The statistical difference was evaluated using ANOVA and Duncan's post-test. Correlation analyses were performed using Spearman's coefficient. Statistical significance was considered when P<0.05. The results did not show a significant difference in BMD between the women with and without fractures. Two bone TA (cluster tendency and variance) were significantly lower in the fracture group. Cluster tendency with VFF in osteopenia was 1.54±1.37 and in osteoporosis was 1.11±58. Cluster tendency without VFF in osteopenia was 2.23±1.38 and in osteoporosis was 1.88±1.14). Variance with VFF in osteopenia was 1.44±1.37 and in osteoporosis was 1.13±59. Variance without VFF in osteopenia was 2.34±1.38 and in osteoporosis was 1.89±1.14. There was a significant correlation between BMD and cluster prominence (r=0.409), cluster tendency (r=0.345), correlation (r=0.570), entropy (r=0.364), information measure corr1 (r=0.378), inverse variance (r=0.449), sum entropy (r=0.320), variance (r=0.338), sum average (r=-0.274), and sum variance (r=-0.266). Our results demonstrated the potential use of TA extracted from routine MRI as a biomarker to assess osteoporosis and identify the tendency of skeletal fragility vertebral fractures.

Lack of relationship between glycemic control and bone mineral density in type 2 diabetes mellitus.

We assessed the effect of chronic hyperglycemia on bone mineral density (BMD) and bone remodeling in patients with type 2 diabetes mellitus. We investigated 42 patients with type 2 diabetes under stable control for at least 1 year, 22 of them with good metabolic control (GMC: mean age = 48.8 +/- 1.5 years, 11 females) and 20 with poor metabolic control (PMC: mean age = 50.2 +/- 1.2 years, 8 females), and 24 normal control individuals (CG: mean age = 46.5 +/- 1.1 years, 14 females). We determined BMD in the femoral neck and at the L2-L4 level (DEXA) and serum levels of glucose, total glycated hemoglobin (HbA1), total and ionic calcium, phosphorus, alkaline phosphatase, follicle-stimulating hormone, intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25-OH-D), insulin-like growth factor I (IGFI), osteocalcin, procollagen type I C propeptide, as well as urinary levels of deoxypyridinoline and creatinine. HbA1 levels were significantly higher in PMC patients (12.5 +/- 0.6 vs 7.45 +/- 0.2% for GMC and 6.3 +/- 0.9% for CG; P < 0.05). There was no difference in 25-OH-D, iPTH or IGFI levels between the three groups. BMD values at L2-L4 (CG = 1.068 +/- 0.02 vs GMC = 1.170 +/- 0.03 vs PMC = 1.084 +/- 0.02 g/cm(2)) and in the femoral neck (CG = 0.898 +/- 0.03 vs GMC = 0.929 +/- 0.03 vs PMC = 0.914 +/- 0.03 g/cm(2)) were similar for all groups. PMC presented significantly lower osteocalcin levels than the other two groups, whereas no significant difference in urinary deoxypyridine was observed between groups. The present results demonstrate that hyperglycemia is not associated with increased bone resorption in type 2 diabetes mellitus and that BMD is not altered in type 2 diabetes mellitus.

Impact of marked weight loss induced by bariatric surgery on bone mineral density and remodeling.

Data about the impact of bariatric surgery (BS) and subsequent weight loss on bone are limited. The objective of the present study was to determine bone mineral density (BMD), bone remodeling metabolites and hormones that influence bone trophism in premenopausal women submitted to BS 9.8 months, on average, before the study (OGg, N = 16). The data were compared to those obtained for women of normal weight (CG, N = 11) and for obese women (OG, N = 12). Eight patients in each group were monitored for one year, with the determination of BMD, of serum calcium, phosphorus, magnesium, parathyroid hormone, 25-hydroxyvitamin D, insulin-like growth factor-I (IGF-I) and osteocalcin, and of urinary calcium and deoxypyridinoline. The biochemical determinations were repeated every three months in the longitudinal study and BMD was measured at the end of the study. Parathyroid hormone levels were similar in the three groups. IGF-I levels (CG = 332 +/- 62 vs OG = 230 +/- 37 vs OGg = 128 +/- 19 ng/mL) were significantly lower in the operated patients compared to the non-operated obese women. Only OGg patients presented a significant fall in BMD of 6.2% at L1-L4, of 10.2% in the femoral neck, and of 5.1% in the forearm. These results suggest that the weight loss induced by BS is associated with a significant loss of bone mass even at sites that are not influenced by weight overload, with hormonal factors such as IGF-I being associated with this process.

Hashtag bone: detrimental effects on bone contrast with metabolic benefits one and five years after Roux-en-Y gastric bypass

Bone loss is a potential adverse consequence of rapid and sustained weight loss after bariatric surgery. The aim of the present study was to evaluate the bone mass, body fat distribution, and metabolic parameters in women submitted to Roux-en-Y gastric bypass (RYGB). The study included the following three groups: one group of lean women (control [C] group) and two groups of obese women, one evaluated one year (B1) and the other five years (B5) after RYGB. Dual-energy X-ray absorptiometry and magnetic resonance imaging were used to determine bone mineral density (BMD; lumbar spine, total hip, and femoral neck) and abdominal fat content (subcutaneous [SAT] and visceral [VAT] adipose tissues, and intrahepatic lipids [IHL]). The BMD/body mass index ratio was lower in the B5 compared with the C group at all sites. Serum C-terminal telopeptide of type I collagen (CTX) levels were higher in the B1 and B5 groups compared with the C group. Individuals submitted to RYGB showed greater SAT but similar VAT and IHL values compared with those in the C group. However, the B5 group had higher mean parathyroid hormone levels compared with the other two groups. Individuals submitted to RYGB presented increased levels of CTX and low BMD for body weight than those in the C group, suggesting that bone catabolism is a persistent alteration associated with RYGB. In conclusion, the long-lasting metabolic benefits obtained with RYGB in obesity are counterbalanced by a persistent catabolic effect of the procedure on bone and mineral metabolism.

Impact of congenital calcitonin deficiency due to dysgenetic hypothyroidism on bone mineral density.

The objective of the present study was to determine the effect of chronic calcitonin deficiency on bone mass development. The results of 11 patients with thyroid dysgenesis (TD) were compared to those of 17 normal individuals (C) and of 9 patients with other forms of hypothyroidism (OH): 4 with hypothyroidism due to inborn errors of thyroid hormone synthesis and 5 with Hashimoto's thyroiditis. The subjects received an intravenous calcium stimulus and blood was collected for the determination of ionized calcium (Ca2+), calcitonin, and intact parathyroid hormone. Bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry. After calcium administration the levels of Ca2+ in the two groups of hypothyroidism were significantly higher than in the normal control group (10 min after starting calcium infusion: C=1.29 +/- 0.08 vs TD=1.34 +/- 0.03 vs OH=1.34 +/- 0.02 mmol/l; P<0.05), and only the TD group showed no calcitonin response (5 min after starting calcium infusion: C = 27.9 5.8 vs TD = 6.6 0.3 vs OH = 43.0 13.4 ng/l). BMD values did not differ significantly between groups (L2-L4: C=1.116 +/- 0.02 vs TD=1.109 +/- 0.03 vs OH=1.050 +/- 0.04 g/cm2). These results indicate that early deficiency of calcitonin secretion has no detrimental effect on bone mass development. Furthermore, the increased calcitonin secretion observed in patients with inborn errors of thyroid hormone biosynthesis does not confer any advantage in terms of BMD.

Parathyroid hormone secretion in chronic human endogenous hypercortisolism.

Osteoporosis is a common manifestation of Cushing's syndrome, but the mechanisms responsible for this abnormality have not been defined. With the objective of analyzing parathyroid hormone (PTH) secretion in chronic hypercortisolism (CH), we evaluated 11 healthy subjects and 8 patients with CH, 6 with Cushing's disease and 2 with adrenal adenoma. These volunteers were submitted to tests of PTH stimulation through hypocalcemia (EDTA), PTH suppression through hypercalcemia (iv and oral calcium), and evaluation of bone mineral density (BMD) by DEXA. During the test of PTH stimulation, the calcium and magnesium concentrations of the normal and CH groups were similar. Patients with CH showed an increased PTH response to the hypocalcemic stimulus compared to controls. PTH values were significantly higher in the CH group at 70 (17.5 +/- 3.5 vs 10.2 +/- 1.3 pmol/l, P = 0.04), and 120 min (26.1 +/- 5.9 vs 11.3 +/- 1.9 pmol/l, P = 0.008) of EDTA infusion. The area under the curve for PTH during EDTA infusion was also significantly higher in patients with CH than in normal subjects (1867 +/- 453 and 805 +/- 148 pmol l(-1) 2 h(-1), P = 0.02). During the test of PTH suppression, calcium, magnesium and PTH levels of the patients with hypercortisolism and controls were similar. BMD was decreased in patients with hypercortisolism in the spine (0.977 +/- 0.052 vs 1.205 +/- 0.038 g/cm2 in controls, P<0.01). In conclusion, our results show that subjects with CH present decreased bone mass mainly in trabecular bone. The use of dynamic tests permitted the detection of increased PTH secretion in response to a hypocalcemic stimulus in CH patients that may probably be involved in the occurrence of osteoporosis in this state.

Resistance to thyroid hormone due to mutations in the THRB gene impairs bone mass and affects calcium and phosphorus homeostasis.

CONTEXT: Resistance to thyroid hormone (RTH) is an inherited syndrome of reduced tissue responsiveness to thyroid hormone, which is usually due to mutations in the thyroid hormone receptor ß gene (THRB). Few studies have been conducted to investigate bone and mineral metabolism in RTH. OBJECTIVE: The objective of the study was to evaluate the clinical and biochemical parameters related to bone and mineral metabolism in RTH due to mutations in the THRB gene (RTHß). DESIGN AND PARTICIPANTS: We conducted a cross-sectional study on 14 patients with RTHß (RTHG), eight adults and six children, and 24 control subjects (CG). OUTCOMES: Serum measures included total calcium (TCa), inorganic phosphate (iP), alkaline phosphatase (AP), parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD), osteocalcin (OC), carboxyterminal telopeptide (CTX), and fibroblast growth factor 23 (FGF-23). We estimated the renal threshold phosphate concentration (TmPO4/GFR) and assessed bone mass using dual X-ray absorptiometry. RESULTS: Adults and children with RTH showed higher serum levels of TCa than controls (P=.029 and, P=.018 respectively). However, only children with RTH exhibited lower serum levels of iP than controls (P=.048). FGF-23 was higher in RTHß children (P=.04). RTHß adults had lower whole-body (P=.01) and lumbar spine (P=.01) bone mineral density than control subjects. The same pattern was observed when the results were expressed as Z-scores between groups, with a lower value in RTHG than in CG for the lumbar spine of adults (P=.03). No difference was observed between groups in PTH, 25OHD, AP, OC, and CTX. CONCLUSION: Biochemical abnormalities are seen in children with RTH (Low iP, high FGF23), while high calcium (with normal UCa) is seen in RTH subjects of all ages, and later on, in adult life, low BMD is seen. Considering that the TRα1 isoform is the predominant TR in the skeleton, we hypothesize that probably these patients may exhibit enhanced calcium flux from bone to circulation. Our data represent a challenge for new studies to unveil the control of calcium and phosphorus homeostasis and fracture risk in these patients.

Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in Wistar rats.

Osteoporosis is a major complication of chronic cholestatic liver disease (CCLD). We evaluated the efficacy of using disodium pamidronate (1.0 mg/kg body weight) for the prevention (Pr) or treatment (Tr) of cholestasis-induced osteoporosis in male Wistar rats: sham-operated (Sham = 12); bile duct-ligated (Bi = 15); bile duct-ligated animals previously treated with pamidronate before and 1 month after surgery (Pr = 9); bile duct-ligated animals treated with pamidronate 1 month after surgery (Tr = 9). Rats were sacrificed 8 weeks after surgery. Immunohistochemical expression of IGF-I and GH receptor was determined in the proximal growth plate cartilage of the left tibia. Histomorphometric analysis was performed in the right tibia and the right femur was used for biomechanical analysis. Bone material volume over tissue volume (BV/TV) was significantly affected by CCLD (Sham = 18.1 ± 3.2 vs Bi = 10.6 ± 2.2%) and pamidronate successfully increased bone volume. However, pamidronate administered in a preventive regimen presented no additional benefit on bone volume compared to secondary treatment (BV/TV: Pr = 39.4 ± 12.0; Tr = 41.2 ± 12.7%). Moreover, the force on the momentum of fracture was significantly reduced in Pr rats (Sham = 116.6 ± 23.0; Bi = 94.6 ± 33.8; Pr = 82.9 ± 22.8; Tr = 92.5 ± 29.5 N; P < 0.05, Sham vs Pr). Thus, CCLD had a significant impact on bone histomorphometric parameters and pamidronate was highly effective in increasing bone mass in CCLD; however, preventive therapy with pamidronate has no advantage regarding bone fragility.